Project description:To identify genes heretofore undiscovered as critical players in the biogenesis of teeth, we have used microarray gene expression analysis of the developing mouse molar tooth (DMT) between 1 and 10 days postnatal to identify genes differentially expressed when compared to 16 control tissues (GEO accession # GSE1986). Of the top 100 genes exhibiting increased expression in the DMT, 29 were found to have been previously associated with tooth development. Differential expression of the remaining 71 genes not previously associated with tooth development was confirmed by qRT-PCR analysis. Further analysis of seven of the latter genes by mRNA in situ hybridization found that five were specific to the developing tooth in the craniofacial region (Rspo4, Papln, Amtn, Gja1, Maf). Of the remaining two, one was found to be more widely expressed (Sp7) and the other was found to be specific to the nasal serous gland, which is close to, but distinct from, the developing tooth (Vrm). Keywords: tooth development
Project description:Mammalian tooth development proceeds through two principal stages—crown formation and root development—driven by intricate interactions between the oral epithelium and neural crest–derived mesenchyme. After crown formation, root development is guided by Hertwig’s epithelial root sheath (HERS), during which Gli1⁺ mesenchymal stem cells (MSCs) give rise to dental pulp, dentin, cementum, and the periodontal ligament (PDL). The root anchors the tooth to alveolar bone via PDL fibers, forming a dynamic occlusal buffer that mediates mechanosensation and nutrient supply. While previous work has shown that macrophages are abundant in the dental pulp and follicle, the functional importance of macrophages in tooth development has not been well characterized. Here, we examined the dynamically changing macrophage populations, labelled by CD68, F4/80, CD206 and other markers, in molars and surrounding tissues during root development in early postnatal mice. We also tracked the dynamic distribution of osteoclasts during tooth development. Importantly, selective depletion of macrophages using clodronate liposomes led to shortened tooth root, impaired PDL elongation and retarded alveolar bone shooting surrounding the root. Gli1⁺ MSCs exhibited increased proliferation but delayed differentiation upon macrophage depletion. Single-cell RNA sequencing and in vitro co-culture experiments support a model in which macrophage-derived TGF-β acts on mesenchymal TGF-β receptors to direct MSC fate and thereby regulate root morphogenesis. Collectively, these findings establish macrophages as critical niche components that orchestrate tooth root development through immune–mesenchymal crosstalk.
Project description:Numerous genes that play important regulative roles during tooth development in mice have been identified. However, very little is known about gene expression and function in human odontogenesis. We used microarrays to detail the global programme of gene expression underlying tooth development and identified distinct classes of up-regulated genes during in the tooth germs. Tooth germs of molar, incisor, and canine at the cap stage were dissected, respectively, from 12-week-old human embryonic oral cavity for RNA extraction and hybridization on Affymetrix microarrays. We sought to screen for the genes that are strongly expressed in the dental tissues and analysis if these genes related to mammalian tooth development and tooth abnormalities.
Project description:Numerous genes that play important regulative roles during tooth development in mice have been identified. However, very little is known about gene expression and function in human odontogenesis. We used microarrays to detail the global programme of gene expression underlying tooth development and identified distinct classes of up-regulated genes during in the tooth germs.